Lecture 24: Cellular immunity and histocompatibility

Question 1

Where is the immature thymocyte produced?

Answer 1

In the bone marrow

Question 2

Where does the thymocyte develop?

Answer 2

In the thymus

Question 3

What cells do the thymocytes form?

Answer 3

The immature thymocyte (shows CD4 and CD8) antigens forms the cytotoxic T lymphocyte (CD8) and helper T lymphocyte (CD4)

Question 4

What are the types of T helper lymphocytes?

Answer 4

Treg - regulate immune response
Th1 - drive cellular immunity
Th2- cause B cells to make antibodies
Th17- innate response - generates inflammatory response

Question 5

Where is the thymus located?

Answer 5

On top of pericardium above the heart

Question 6

What is the role of the thymus in maturation of T lymphocytes?

Answer 6

The progenitor lymphoid cells are educated to recognise self MHC molecules

In this process many die from neglect

Question 7

How does the body detect cells that have been infected with a virus?

Answer 7

Viral peptide is displayed as part of the major histocompatibility complex (MHC)

Question 8

What is MHC?

Answer 8

Major histocompatibility complex is a set of highly polymorphic genes that code for human leukocyte antigens on the cell surface

Question 9

How do killer T lymphocytes kill infected cells?

Answer 9

Cytotoxic T cells react to cells in the body when there is a change in MHC class I molecules - these will express a neo-antigen (viral or altered self antigen)

Question 10

How was the existence of the MHC gene proven?

Answer 10

Formation of congenic strains of mouse by breeding a child (AB) to its parent (A or B) multiple times - only those offspring who rejected tissue transplants were continually bred.

This meant that the congenic mouse basically had the same genetics as their parent except for the one gene - MHC

T lymphocytes were extracted from these mice and its reaction with infected cells were observed

The T lymphocytes only recognised cells from its own strain proving the existence of this MHC

Question 11

What is MHC restriction?

Answer 11

The idea that viral immunity requires presence and recognition of two antigens

Self - antigen encoded by MHC
Non-self - antigen encoded by virus

Question 12

What is HLA?

Answer 12

Human leukocyte antigen - the surface antigen on body cells coded for by the MHC. These present peptide antigens to T cells

There are 6 different molecules that are expressed
Class I - A B C
Class II - DR DP DQ

Question 13

What is CD4 and CD8?

Answer 13

Accessory molecules on T cells that physically associate with the T cell receptor

Question 14

Where is CD4 found?

Answer 14

These are found associated with T cell receptors of helper T cells and recognize antigens in MHC class II

Question 15

Where is CD8 found?

Answer 15

These molecules are found associated with T cell receptors of cytotoxic T cells and recognise antigens in MHC class I

Question 16

What is the function of CD4 and CD8?

Answer 16

They have cytoplasmic tails associated with intracellular tyrosine kinases which allow them to initiate T cell signaling through activation of the phosphorylation cascade. Hence, they play an important role in activation of adaptive immune response

Question 17

What do helper T cells do?

Answer 17

T cells proliferate and produce cytokines that help other cells

Question 18

What do cytotoxic T cells do?

Answer 18

Produces granzyme and perforins that punch holes in the target cell membrane and destroy cell viability

Question 19

What is the difference between MHC class I and II?

Answer 19

MHC Class I codes for the viral peptide which leads to a response from CD8 causing a cytotoxic response

MHC Class II codes for the bacterial peptide which leads to a response from CD4 causing a helper response

Question 20

What is MHC polymorphism?

Answer 20

The variation of amino acids in the protein domains that form the peptide groove

An individual will express 2 x 3 MHC Class I and 2 x 3 MHC Class molecules - co-dominance (both paternal and maternal genes are expressed)

Question 21

What are 2 consequences of polymorphism?

Answer 21

1. Tissue transplantation is difficult except between identical twins
2. MHC polymorphisms are strongly linked to many autoimmune diseases